The p53-related p73 proteins regulate developmental processes, cell growth, and DNA damage response. p73 function is regulated by post-translational modifications and protein-protein interactions. At the G(2)/M transition, p73 is phosphorylated at Thr-86 by the p34cdc2/cyclin B complex; this is associated with its exclusion from condensed chromosomes and loss of DNA binding and transcriptional activation ability. Here we showed that p73 hypo-phosphorylated species reappear during mitotic exit, concomitant with p73 relocalization to telophase nuclei and recovered ability to activate transcription. Functional knock-out of p73 gene expression by small interfering RNAs ( siRNAs) alters mitotic progression, yielding an increase of ana-telophase cells, the accumulation of aberrant late mitotic figures, and the appearance of abnormalities in the subsequent interphase. This p73 activity at the M-to-G(1) transition is mediated by its transactivating function because expression of the transcription dominant negative mutant p73DD induces the same mitotic exit phenotype. We also found that the cyclin-dependent kinase inhibitor Kip2/p57 gene is a specific target of p73 regulation during mitotic exit and re-entry into G(1). Both knock-out of p73 gene expression by siRNAs and abrogation of p73-dependent transcription by the p73DD mutant abrogate Kip2/p57 increase at the M-to-G(1) transition. Moreover, similar abnormalities ( e. g. delay in late mitotic stages with the accumulation of aberrant ana-telophase figures, and abnormalities in the following interphase) are observed in cultures in which the expression of Kip2/p57 is abrogated by siRNAs. These results identify a novel p73-Kip2/p57 pathway that coordinates mitotic exit and transition to G(1).

Merlo, P., Fulco, M., Costanzo, A., Mangiacasale, R., Strano, S., Blandino, G., et al. (2005). A role of p73 in mitotic exit. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 280(34), 30354-30360 [10.1074/jbc.M500635200].

A role of p73 in mitotic exit

COSTANZO, ANTONIO;
2005-01-01

Abstract

The p53-related p73 proteins regulate developmental processes, cell growth, and DNA damage response. p73 function is regulated by post-translational modifications and protein-protein interactions. At the G(2)/M transition, p73 is phosphorylated at Thr-86 by the p34cdc2/cyclin B complex; this is associated with its exclusion from condensed chromosomes and loss of DNA binding and transcriptional activation ability. Here we showed that p73 hypo-phosphorylated species reappear during mitotic exit, concomitant with p73 relocalization to telophase nuclei and recovered ability to activate transcription. Functional knock-out of p73 gene expression by small interfering RNAs ( siRNAs) alters mitotic progression, yielding an increase of ana-telophase cells, the accumulation of aberrant late mitotic figures, and the appearance of abnormalities in the subsequent interphase. This p73 activity at the M-to-G(1) transition is mediated by its transactivating function because expression of the transcription dominant negative mutant p73DD induces the same mitotic exit phenotype. We also found that the cyclin-dependent kinase inhibitor Kip2/p57 gene is a specific target of p73 regulation during mitotic exit and re-entry into G(1). Both knock-out of p73 gene expression by siRNAs and abrogation of p73-dependent transcription by the p73DD mutant abrogate Kip2/p57 increase at the M-to-G(1) transition. Moreover, similar abnormalities ( e. g. delay in late mitotic stages with the accumulation of aberrant ana-telophase figures, and abnormalities in the following interphase) are observed in cultures in which the expression of Kip2/p57 is abrogated by siRNAs. These results identify a novel p73-Kip2/p57 pathway that coordinates mitotic exit and transition to G(1).
2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/35 - MALATTIE CUTANEE E VENEREE
English
Con Impact Factor ISI
Cells; DNA; Phosphorus; RNA; Cell growth; Kinase inhibitor; Mitosis; Small interfering RNA (siRNA); Proteins; cyclin dependent kinase 1; cyclin dependent kinase inhibitor; DNA; protein p53; protein p57; protein p73; small interfering RNA; threonine; anaphase; animal cell; article; cell cycle G1 phase; cell growth; chromosome condensation; controlled study; DNA damage; gene expression regulation; mitosis; nonhuman; phase transition; phenotype; priority journal; protein analysis; protein modification; protein phosphorylation; protein processing; protein protein interaction; telophase; transcription regulation; Anaphase; CDC2 Protein Kinase; Cell Cycle; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Cell Separation; Chromosomes; Cyclin B; Cyclin-Dependent Kinase Inhibitor p57; DNA Damage; DNA-Binding Proteins; Flow Cytometry; G1 Phase; Genes, Dominant; Genes, Tumor Suppressor; Glioma; Humans; Mitosis; Mutation; Nuclear Proteins; Phenotype; Phosphorylation; Plasmids; Protein Structure, Tertiary; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Small Interfering; Telophase; Threonine; Time Factors; Trans-Activation (Genetics); Transcription, Genetic; Tumor Suppressor Protein p53; Tumor Suppressor Proteins
Merlo, P., Fulco, M., Costanzo, A., Mangiacasale, R., Strano, S., Blandino, G., et al. (2005). A role of p73 in mitotic exit. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 280(34), 30354-30360 [10.1074/jbc.M500635200].
Merlo, P; Fulco, M; Costanzo, A; Mangiacasale, R; Strano, S; Blandino, G; Taya, Y; Lavia, P; Levrero, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34275
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